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Hard-x-ray region tomographic reconstruction of the refractive-index gradient vector field: imaging principles and comparisons with diffraction-enhanced-imaging-based computed tomography.

The unique tomographic imaging method based on refractive effects that was recently developed by Maksimenko et al. [Appl. Phys. Lett. 86, 124105 (2005)] exhibits an excellent imaging property in the hard-x-ray region for phase objects such as soft materials and biological samples. However, there seems to have been little consideration of the physical aspects of the underlying imaging principles. Also, as the method is similar to diffraction-enhanced-imaging (DEI)-based computed tomography (CT), the difference between these two methodologies has not been made clear. We theoretically consider the imaging principles starting from the measurement process to the reconstruction procedures from the viewpoint of geometrical optics and then clarify their difference in relationship to the physical quantities to be depicted. The major feature of this novel method is the in-plane two-dimensional vector-field reconstruction of the refractive-index gradient in an object, while DEI CT obtains the out-of-plane scalar-field gradient component. In other words, the novel method and DEI CT present the transverse and the longitudinal components, respectively, of the three-dimensional vector fields of the gradient refractive index. Therefore they can be considered complementary to each other.

Algorithms↗

Computer-generated microsurgical anatomy of the basilar artery bifurcation. Technical note.

The authors' goal was to develop a computer graphics model to represent the microsurgical anatomy of the basilar artery (BA) bifurcation and surrounding structures to simulate surgery of a BA bifurcation aneurysm performed via the transsylvian approach. The source of the input data was a variety of publications that showed detailed anatomy of the area. A computer graphics model of the area near the BA bifurcation including relevant structures, such as perforating branches or cranial nerves, was depicted in detail. A BA bifurcation aneurysm was added to the computer graphics model and it was rotated to simulate the transsylvian approach. After the internal carotid artery was displaced using a virtual retractor, the aneurysm was exposed, thus providing an understanding of the three-dimensional surgical orientation of the area. Designing a standard anatomical model on the basis of data culled from a variety of publications and adding morphological changes by using a virtual retractor to displace structures that obstruct the view along a critical path at the base of the brain are useful strategies of computer manipulation for surgical simulation in open microneurosurgery. This methodological tool would be useful in teaching surgical microanatomy and in introducing a new navigational system for virtual reality. Both concept and technical details are discussed.

Basilar Artery↗

Algorithms for the computation of solutions of the Ornstein-Zernike equation.

We introduce a robust and efficient methodology to solve the Ornstein-Zernike integral equation using the pseudoarc length (PAL) continuation method that reformulates the integral equation in an equivalent but nonstandard form. This enables the computation of solutions in regions where the compressibility experiences large changes or where the existence of multiple solutions and so-called branch points prevents Newton's method from converging. We illustrate the use of the algorithm with a difficult problem that arises in the numerical solution of integral equations, namely the evaluation of the so-called no-solution line of the Ornstein-Zernike hypernetted chain (HNC) integral equation for the Lennard-Jones potential. We are able to use the PAL algorithm to solve the integral equation along this line and to connect physical and nonphysical solution branches (both isotherms and isochores) where appropriate. We also show that PAL continuation can compute solutions within the no-solution region that cannot be computed when Newton and Picard methods are applied directly to the integral equation. While many solutions that we find are new, some correspond to states with negative compressibility and consequently are not physical.

Journal Article↗

Maximum likelihood fitting of FROC curves under an initial-detection-and-candidate-analysis model.

We have developed a model for FROC curve fitting that relates the observer's FROC performance not to the ROC performance that would be obtained if the observer's responses were scored on a per image basis, but rather to a hypothesized ROC performance that the observer would obtain in the task of classifying a set of "candidate detections" as positive or negative. We adopt the assumptions of the Bunch FROC model, namely that the observer's detections are all mutually independent, as well as assumptions qualitatively similar to, but different in nature from, those made by Chakraborty in his AFROC scoring methodology. Under the assumptions of our model, we show that the observer's FROC performance is a linearly scaled version of the candidate analysis ROC curve, where the scaling factors are just given by the FROC operating point coordinates for detecting initial candidates. Further, we show that the likelihood function of the model parameters given observational data takes on a simple form, and we develop a maximum likelihood method for fitting a FROC curve to this data. FROC and AFROC curves are produced for computer vision observer datasets and compared with the results of the AFROC scoring method. Although developed primarily with computer vision schemes in mind, we hope that the methodology presented here will prove worthy of further study in other applications as well.

Algorithms↗

Methodological challenges in studying recurrence of low back pain.

Recurrences of low back pain (LBP) have been shown to be both frequent and costly, with reported recurrence rates ranging from 5 to 82%. Numerous methodological approaches have been developed to identify recurrence but there has been no standardized definition of LBP recurrence or required follow-up time. The objective of this study was to compare the methodological approaches used to analyze LBP recurrence in seminal contributions and to describe the differences in definitions of LBP recurrence and follow-up structure. Twelve seminal articles were identified for review during which four types of LBP recurrence definition and two types of follow-up structure were recognized. Definitional and follow-up differences considerably contributed to variations in computed recurrence rates due either to measurement or other methodological shortcomings, such as loss to follow-up and sick person effect. The results suggest that there is a need to develop a standardized definition of LBP recurrence and a standardized approach to follow-up to allow direct comparisons of published research findings. The use of alternative definitions is also likely to impact analyses of risk factors contributing to LBP recurrence and direct and indirect costs associated with treating LBP.

Follow-Up Studies↗

Deconvolution of evoked responses obtained at high stimulus rates.

Continuous loop averaging deconvolution (CLAD) is a new general mathematical theory and method developed to deconvolve overlapping auditory evoked responses obtained at high stimulation rates. Using CLAD, arbitrary stimulus sequences are generated and averaged responses deconvolved. Until now, only a few special stimulus series such as maximum length sequences (MLS) and Legendre sequences (LGS) were capable of performing this task. A CLAD computer algorithm is developed and implemented in an evoked potential averaging system. Computer simulations are used to verify the theory and methodology. Auditory brainstem responses (ABR) and middle latency responses (MLR) are acquired from subjects with normal hearing at high stimulation rates to validate and show the feasibility of the CLAD technique.

Acoustic Stimulation↗

CT colonography in the detection of colorectal polyps and cancer: systematic review, meta-analysis, and proposed minimum data set for study level reporting.

PURPOSE: To assess the methodologic quality of available data in published reports of computed tomographic (CT) colonography by performing systematic review and meta-analysis. MATERIALS AND METHODS: The MEDLINE database was searched for colonography reports published between 1994 and 2003, without language restriction. The terms colonography, colography, CT colonoscopy, CT pneumocolon, virtual colonoscopy, and virtual endoscopy were used. Studies were selected if the focus was detection of colorectal polyps verified with within-subject reference colonoscopy by using key methodologic criteria based on information presented at the Fourth International Symposium on Virtual Colonoscopy (Boston, Mass). Two reviewers independently abstracted methodologic characteristics. Per-patient and per-polyp detection rates were extracted, and authors were contacted, when necessary. Per-patient sensitivity and specificity were calculated for different lesion size categories, and Forest plots were produced. Meta-analysis of paired sensitivity and specificity was conducted by using a hierarchical model that enabled estimation of summary receiver operating characteristic curves allowing for variation in diagnostic threshold, and the average operating point was calculated. Per-polyp sensitivity was also calculated. RESULTS: Of 1398 studies considered for inclusion, 24 met our criteria. There were 4181 patients with a study prevalence of abnormality of 15%-72%. Meta-analysis of 2610 patients, 206 of whom had large polyps, showed high per-patient average sensitivity (93%; 95% confidence interval [CI]: 73%, 98%) and specificity (97%; 95% CI: 95%, 99%) for colonography; sensitivity and specificity decreased to 86% (95% CI: 75%, 93%) and 86% (95% CI: 76%, 93%), respectively, when the threshold was lowered to include medium polyps. When polyps of all sizes were included, studies were too heterogeneous in sensitivity (range, 45%-97%) and specificity (range, 26%-97%) to allow meaningful meta-analysis. Of 150 cancers, 144 were detected (sensitivity, 95.9%; 95% CI: 91.4%, 98.5%). Data reporting was frequently incomplete, with no generally accepted format. CONCLUSION: CT colonography seems sufficiently sensitive and specific in the detection of large and medium polyps; it is especially sensitive in the detection of symptomatic cancer. Studies are poorly reported, however, and the authors propose a minimum data set for study reporting.

Colonic Polyps↗

Teaching paediatric residents about learning disorders: use of standardised case discussion versus multimedia computer tutorial.

BACKGROUND: We developed a standardised case-based educational exercise on the topic of childhood learning disorders, and a multimedia computerised adaptation of this exercise, as part of a national curriculum project based on the Bright Futures guidelines. OBJECTIVE: To explore resident perceptions of the facilitated case discussion (FCD) and the computerised tutorial (CT). DESIGN: Quasi-randomised comparison of two educational interventions. SETTING: Preclinic teaching conferences at a large urban children's hospital. PARTICIPANTS: A total of 46 paediatric residents years 1-3 assigned to either FCD (n = 21) or CT (n = 25). INTERVENTIONS: FCD residents met in groups of 8-12 with a trained facilitator for a structured case discussion, while CT residents worked in groups of 2-3 at a computer station linked to an interactive website. OUTCOME MEASURES: Participant responses during semistructured focus group interviews. ANALYSIS: Focus group transcripts, field notes and computer logs were analysed simultaneously using qualitative grounded theory methodology. RESULTS: Residents experienced CT as fun, offering flexibility, greater auditory and visual appeal and more opportunities for active learning. FCD allowed greater contact with expert faculty and made the material more relevant to clinical practice. FCD participants emphasised the clinical skills gleaned and stated that the learning experience would change their future patient management. Both groups reported that case discussion was more interactive than computer learning. Median time spent on learning was slightly shorter for the CT group. All groups of learners arrived at the correct final diagnosis. CONCLUSIONS: FCD and CT stimulate different types of learning among paediatric residents. Future studies are needed to determine how to integrate these two techniques to meet the learning needs of residents in diverse settings.

Boston↗

[Helping physicians arrive at medical diagnoses: how and why (author's transl)].

In the majority of the medical disciplines the diagnosis still constitutes the corner-stone of medicine. Every year this function becomes increasingly difficult and time-consuming and it is felt that the doctor should be able to benefit easily and rapidly from the most recent findings. A simple analysis of the natural process of decision-making, followed by a critical inventory of the various methods used to diagnose, has led us to develop our method for computer-assisted diagnosis (ADM). In our presentation of the methodology of diagnostic decision-making we examine the natural process, the analytical and synthetic methods as well as the difficulties and errors liable to occur. Four methods used in arriving at a diagnosis are analysed and criticized: those based on probability, those based on pattern recognition, those based on logic, and those based on classification methods. Finally a case is made for a computer-assisted diagnostic system based on a logical method of the documentation type.

Decision Making↗

PC-based application programs in large health care systems.

Public health care agencies lack the infrastructure to meet the increasing operational demands on them, but there is little comparative data on alternative operational structures and systems from which to formulate remedies. Improved information management systems could help address both the workload and the gathering of critically needed data. PC-based database and application programs (PC-APs) that communicate with the mainframe are proposed as a methodology for filling the information-processing gap between mainframe computing and manual information systems. We also propose a model for systematic study of information management systems in clinical settings which can be used to evaluate other aspects of clinical program operations as well. A pilot study demonstrating these methodologies suggests that this is a fruitful approach to assessing ambulatory care operations and that PC-APs can improve administrative and clinical functions and enhance FTE productivity at lower overall cost.

Ambulatory Care Information Systems↗

Single-step stereolithography of complex anatomical models for optical flow measurements.

Transparent stereolithographic rapid prototyping (RP) technology has already demonstrated in literature to be a practical model construction tool for optical flow measurements such as digital particle image velocimetry (DPIV), laser doppler velocimetry (LDV), and flow visualization. Here, we employ recently available transparent RP resins and eliminate time-consuming casting and chemical curing steps from the traditional approach. This note details our methodology with relevant material properties and highlights its advantages. Stereolithographic model printing with our procedure is now a direct single-step process, enabling faster geometric replication of complex computational fluid dynamics (CFD) models for exact experimental validation studies. This methodology is specifically applied to the in vitro flow modeling of patient-specific total cavopulmonary connection (TCPC) morphologies. The effect of RP machining grooves, surface quality, and hydrodynamic performance measurements as compared with the smooth glass models are also quantified.

Blood Flow Velocity↗

Cox regression analysis of multivariate failure time data: the marginal approach.

Multivariate failure time data are commonly encountered in scientific investigations because each study subject may experience multiple events or because there exists clustering of subjects such that failure times within the same cluster are correlated. In this paper, I present a general methodology for analysing such data, which is analogous to that of Liang and Zeger for longitudinal data analysis. This approach formulates the marginal distributions of multivariate failure times with the familiar Cox proportional hazards models while leaving the nature of dependence among related failure times completely unspecified. The baseline hazard functions for the marginal models may be identical or different. Simple estimating equations for the regression parameters are developed which yield consistent and asymptotically normal estimators, and robust variance-covariance estimators are constructed to account for the intra-class correlation. Simulation results demonstrate that the large-sample approximations are adequate for practical use and that ignoring the intra-class correlation could yield rather misleading variance estimators. The proposed methodology has been fully implemented in a simple computer program which also incorporates several alternative approaches. Detailed illustrations with data from four clinical or epidemiologic studies are provided.

Adolescent↗

A decision class analysis of critical care life-support decision-making.

Decision analysis is a powerful methodology that can help clinicians make good decisions. Because it is not practical to place a decision analyst at the bedside in critical care units, the application of this methodology will require leveraging the analyst through computer-based systems. A decision class analysis is a collective analysis of a group of decisions that provides the high-level specification for such a computer system. This paper presents a decision class analysis of critical care life-support decisions. Key elements of this analysis are: the simplification of an otherwise extremely complex multistage sequential decision problem by using a sequence of two-stage models, and the use of six generic knowledge maps that capture the extremely complex relevant medical knowledge.

Artificial Intelligence↗

[Recommendations for the use of hospital statistics for hospital planning and management].

The trend towards DRGs (Diagnosis Related Groups) represents a major step in the development of hospital information systems. Based on the experience with the use of routine hospital data in the Swiss DRG project, this article presents recommendations in five areas: 1. Data collection and coding of medical routine data in hospitals 2. Continuous monitoring of the computer algorithm used to group diagnoses ("Grouper") 3. Methodology of calculating costs 4. Use of DRGs in planning and management; and finally 5. Strategies to implement these recommendations

Algorithms↗

Diagnostic utility of oncogenes and their products in human cancer.

The first clear cut association of an oncogene with a specific cancer is the c-abl translocation in chronic myelogenous leukemia and acute lymphocytic leukemia; it has been observed in 90% of CML cases examined. This is the major contributing factor to its being the target of the first oncogene-based FDA-approved diagnostic test. Although the role of the abl translocation in the tumorigenic process is not yet understood, it is clear that somehow it must be causally related to the disease, and thus is an ideal target for a diagnostic test. The association of this oncogene with a specific cancer is the model on which all others may be based in the future. Second generation tests could easily include PCR on mRNA, and/or in situ hybridization, both of which could be performed using blood samples. Both methods would provide a faster means of testing a large number of cells, however, the methodologies must be improved through automation and computer-aided image analysis, respectively, in order to become useful routine tests. Both neu and epidermal growth factor receptor (EGFR) appear to have a close correlation between overexpression of the gene product and outcome of disease in breast cancer; valuable information for prognosis of the disease. And again, although the actual mechanism of action of these molecules and how this relates to the tumorigenic process is not yet known, it is believed from the very nature of the molecules that they must in some way contribute to the progression of the disease. In both cases, the protein products are overexpressed in tissue, and in the case of Neu, it appears as through at least some of the patients have a Neu-related protein in their serum. These molecules present relatively easy targets for the development of diagnostic/prognostic assays, as antibodies are easily made and can be incorporated into a variety of assay formats. Current assays available, an ELISA for Neu and a radio-ligand binding assay for EGFR, are highly sensitive, reproducible and relatively easy to perform. Only the ELISA is commercially available, however, and hence allows for easy comparison between laboratories. An abvious step towards the routine measurement of EGFR then is the development of a comparable commercially available test. An improvement for both types of assay would be the incorporation of an internal control to gauge the cellular component of the tissue samples that are tested. The outcome of the applications of myc and ras to cancer diagnostics is not so easily predictable, with a couple of exceptions.(ABSTRACT TRUNCATED AT 400 WORDS)

Female↗

Results of IAEA intercomparisons in the frame of indirect methods for assessing intakes of radionuclides.

The IAEA safety activities to support the assessment of occupational exposure due to intake of radionuclides through a comprehensive set of Safety Guides, Safety Reports and other documents will soon be completed. The future IAEA activities in this field will focus more on training and international intercomparisons. In recent years extensive development in measurement techniques, phantoms and computational tools have occurred. Determination of the radionuclide activity in the body or excreta, the intake and the resulting internal dose can, therefore, be approached in many different ways, depending on the amount and quality of the data, the skill of the dosimetrist, computational tools available, the assumptions made and the methodology used. Thus, it is important for laboratories involved in internal dosimetry to undergo performance-testing procedures to demonstrate the correctness of the methods applied and also the consistency of their results with those obtained by other laboratories. Several intercomparison exercises were organized by the IAEA on the determination of radionuclides in human urine samples. These previous intercomparison exercises revealed significant differences in the approaches, methods and assumptions, and consequently in the results. This underlined the importance of this kind of intercomparison programmes as a key element of the harmonization process. The purpose of this paper is to present the current and future IAEA activities in support of assessment of occupational exposure due to intakes of radionuclides by organizing intercomparison runs focused on indirect methods for assessing intakes as well as the recommendations for setting up a Quality Management Systems for technical services in radiation safety.

International Agencies↗

Algorithmically designed peptides ameliorate behavioral defects in animal model of ADHD by an allosteric mechanism.

This study exemplifies the use of three ADHD-relevant methodological innovations. (1) The use of novel, patented, computational peptide design techniques to generate peptides targeting the extra-cellular and para-transmembrane amino acid loops of the putatively ADHD-involved, D(2) dopamine receptor, D(2)DAR; (2) experimental evidence that these peptides in L-amino acid/ortho ordered or D-amino acid/reverse ordered (retro-inverso), D(2)DAR, hydrophobic eigenmode matched forms, evoked positive allosteric and indirect agonist influences on in vitro stably receptor transfected CHO and LtK cells and on in vivo, brain mediated activity; (3) a representative 15 residue all-D-amino acid, D(2) mode matched peptide, given parenterally, was found to "repair" a key aberrant ADHD behavioral characteristic in a standard animal model of ADHD, the Spontaneously Hypertensive Rat, SHR, relative to its progenitor species control, the Wistar-Kyoto rat, WKY. The representative, retro-inverso peptide, all-D-LLYKNKPRYPKRNRE, reversed SHR's relative deficiency in sensory motor gating (pre-pulse inhibition, PPI) while leaving SHR's nonselective attention (rearings), impulsive behavior (time in center), and activity level (timed total motor behavior) unchanged. Amphetamine also reversed SHRs sensory gating defect, but with significant increases in nonselective attention, impulsivity and hyperactivity. These preliminary results suggest the possibility of a new, "softer" pharmacological approach to ADHD: hydrophobic mode matched peptide allosteric augmentation of the activity of indigenous dopamine with respect to D(2)DAR mediated function, in place of stimulant drug-induced presynaptic dopamine release or impairment of dopamine uptake.

Acoustic Stimulation↗

Properties of MEG tomographic maps obtained with spatial filtering.

Magnetoencephalography (MEG) has, in comparison with other functional imaging modalities, unique properties which makes it the prime candidate for the noninvasive investigation of long-range oscillatory interactions in the human brain. Recent methodological developments based on spatial filtering introduced the computation of functional tomographic maps covering the entire brain and representing the distribution of coherence to a given reference signal or the distribution of power. Because of the spatially inhomogeneous sensitivity profile of the MEG sensors, the spatial resolution of the resulting functional maps is not isotropic across the brain. Here, we introduce a convenient analytic expression for the computation of the spatial resolution at any given point in the brain. We derive the dependence of the resolution on the signal-to-noise ratio and on the changes of the leadfields. The resolution map can be displayed on anatomical MRI in the same way as the functional maps. In addition, we establish a procedure for computing a confidence volume of local maxima which is based on a bootstrap method. The confidence volume is a measure for the uncertainty of the localization. It is important for assigning local maxima of activation to specific anatomical structures and may be used to test for differences in localization between different experimental conditions.

Artifacts↗